NEW CONDENSED BIOACTIVE PYRIMIDINES. SYNTHETIC STRATEGIES, STRUCTURAL CHARACTERIZATION AND BIORATIONAL STUDIES.

Versatile 3-aminopyrrolopyridine-2-carboxylate and -2-carboxylic acid derivatives 2a,bwere obtained based on an orthofunctionalized pyrrole derivative 1. Initially cyclization of ester 2a followed by formylation to obtain a tricyclic chloroaldehyde derivative 4, which on further treatment with hydroxylamine hydrochloride yielded the corresponding oxime5a. The latter product was subsequently dehydrated forming the tricyclic 2-cyanopyrimidine derivative 5b. Other different 2-functionalized tricyclic derivatives of N-3-substituted pyrimidine were synthesized, for biorational assessment, starting from the key precursors 2a,b through convenient methods. All condensed tricyclic pyrimidine derivatives with the common 7,9-diphenyl-8-(4-methoxyphenylazo) substitution patternwere evaluated for their toxicity on the 4th larval instar of the mosquitoes, Culexpipiens. The compounds under investigation displayed different levels of biorational effects. In general, chloro compounds 4, 5a and 5b that have a chlorine atom as a substituent on the C-4 atom of the pyrimidine ring, showed high insecticidal activity, with compound 5b showing essentially the highest biorational effect. The lethal concentration at LC50 of the latter compound 5b is very significant (0.22%). Our results may provide some guidance for development of some novel chloropyrimidine-based insecticidal lead structures. The detailed synthesis and biological screening data were reported.